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The global burden of pneumococcal diseases is high, with young children and adults ≥50 years of age at highest risk of infection. Two types of vaccine are available for the prevention of pneumococcal diseases caused by specific Streptococcus pneumoniae serotypes: the pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccine (PCV7, PCV10, and PCV13). Despite pneumococcal immunization programs in adults and children, the burden in adults has remained high. Most European countries have national or local/regional vaccination recommendations. The objective of this review was to provide an overview of the government recommendations for pneumococcal vaccination outside routine childhood vaccination programs for 16 Western European countries as of August 2014. We found that recommendations for pneumococcal immunization across Europe are complex and vary greatly among countries in terms of age groups and risk groups recommended for vaccination, as well as which vaccine should be administered. Clarifying or simplifying these recommendations and improving their dissemination could help to increase pneumococcal vaccine uptake and decrease the high burden of pneumococcal diseases in adults, both through a direct effect of the vaccine and via a herd effect in unvaccinated individuals.

Pneumococcal carriage is a prerequisite for disease, and underpins herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few data on the impact of PCVs in lower income settings, particularly in Asia. In 2013, the Lao People's Democratic Republic (Lao PDR) introduced 13-valent PCV (PCV13) as a 3 + 0 schedule (doses at 6, 10 and 14 weeks of age) with limited catch-up vaccination. We conducted two cross-sectional carriage surveys (pre- and two years post-PCV) to assess the impact of PCV13 on nasopharyngeal pneumococcal carriage in 5-8 week old infants (n = 1000) and 12-23 month old children (n = 1010). Pneumococci were detected by quantitative real-time PCR, and molecular serotyping was performed using DNA microarray. Post PCV13, there was a 23% relative reduction in PCV13-type carriage in children aged 12-23 months (adjusted prevalence ratio [aPR] 0.77 [0.61-0.96]), and no significant change in non-PCV13 serotype carriage (aPR 1.11 [0.89-1.38]). In infants too young to be vaccinated, there was no significant change in carriage of PCV13 serotypes (aPR 0.74 [0.43-1.27]) or non-PCV13 serotypes (aPR 1.29 [0.85-1.96]), although trends were suggestive of indirect effects. Over 70% of pneumococcal-positive samples contained at least one antimicrobial resistance gene, which were more common in PCV13 serotypes (p < 0.001). In 12-23 month old children, pneumococcal density of both PCV13 serotypes and non-PCV13 serotypes was higher in PCV13-vaccinated compared with undervaccinated children (p = 0.004 and p < 0.001, respectively). This study provides evidence of PCV13 impact on carriage in a population without prior PCV7 utilisation, and provides important data from a lower-middle income setting in Asia. The reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Lao PDR.

Abstract
Gastrin-17 (G-17), pepsinogen-1 (Pg1) and pepsinogen-2 (Pg2) reflect the functional state of gastric mucosa and are used for non-invasive diagnosis and screening of atrophic gastritis. The aim of the study was to clarify if erosive reflux disease (ERD) or non-ERD (NERD) can be distinguished from other dyspeptic conditions in patients, in a non-invasive manner using specific biomarkers. Levels of G-17, Pg1, and Pg2 were measured in 141 ERD patients (median age 48 years, males — 68), 122 NERD patients (median age 45 years, males — 32) and 410 control patients (median age 50 years, males — 97). Levels of biomarkers in ERD and NERD groups were compared to controls. Median levels of G-17 (1.94 vs 2.92 pmol/L, p = 0.036) and Pg2 (6.70 vs 7.79 µg/l, p = 0.046) were lower in the ERD group compared to control patients; no difference with respect to the control was found for the NERD group. After exclusion of the patients having at least one potential condition that might modify the levels of the biomarkers (gastric mucosa atrophy, Helicobacter pylori colonisation), no difference in levels of biomarkers was observed with respect to the control for both the ERD and NERD groups. G-17, Pg1, and Pg2 based tests cannot be used to distinguish ERD or NERD from other dyspeptic conditions in patients.

Chronic liver disease is a late stage of progressive hepatic fibrosis. It consists of functional and structural disruptions in most chronic liver diseases. An accurate diagnosis allows us to establish the degree of fibrosis and the stage of the disease, the prognosis of the patient and to predict a treatment response. Despite the fact that liver biopsy is considered a gold standard, noninvasive methods for diagnosing liver fibrosis have gained more and more importance. Whether we talk about serum biomarkers or imagistic methods from transient elastography to 3-D magnetic resonance elastography, the question remains: are these useful or useless? Serum biomarkers represent blood components that can reflect liver histological changes, thus they can monitor the continuous process of fibrosis. These can be subcategorized in direct (that show extracellular matrix turnover) and indirect markers (that reflect disturbances in the hepatic function). However these markers alone are not as accurate in the staging of fibrosis, only help differentiate patients without or with low grade of fibrosis from those with significant fibrosis and cannot be considered alone in the diagnosis of liver fibrosis. Imagistic methods include: ultrasound-based transient elastography, magnetic resonance elastography (MRE), 2D-shear wave elastography, acoustic radiation impulse imaging (ARFI) and cross sectional imaging, the first being the most used. Using a combination of non-invasive tools allows us to diminish the number of patients in need of liver biopsy. However, the patient must always be informed of the advantages and disadvantages of each method and its limitations.

Pneumococcal carriage is a prerequisite for disease, and underpins herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few data on the impact of PCVs in lower income settings, particularly in Asia. In 2013, the Lao People's Democratic Republic (Lao PDR) introduced 13-valent PCV (PCV13) as a 3 + 0 schedule (doses at 6, 10 and 14 weeks of age) with limited catch-up vaccination. We conducted two cross-sectional carriage surveys (pre- and two years post-PCV) to assess the impact of PCV13 on nasopharyngeal pneumococcal carriage in 5-8 week old infants (n = 1000) and 12-23 month old children (n = 1010). Pneumococci were detected by quantitative real-time PCR, and molecular serotyping was performed using DNA microarray. Post PCV13, there was a 23% relative reduction in PCV13-type carriage in children aged 12-23 months (adjusted prevalence ratio [aPR] 0.77 [0.61-0.96]), and no significant change in non-PCV13 serotype carriage (aPR 1.11 [0.89-1.38]). In infants too young to be vaccinated, there was no significant change in carriage of PCV13 serotypes (aPR 0.74 [0.43-1.27]) or non-PCV13 serotypes (aPR 1.29 [0.85-1.96]), although trends were suggestive of indirect effects. Over 70% of pneumococcal-positive samples contained at least one antimicrobial resistance gene, which were more common in PCV13 serotypes (p < 0.001). In 12-23 month old children, pneumococcal density of both PCV13 serotypes and non-PCV13 serotypes was higher in PCV13-vaccinated compared with undervaccinated children (p = 0.004 and p < 0.001, respectively). This study provides evidence of PCV13 impact on carriage in a population without prior PCV7 utilisation, and provides important data from a lower-middle income setting in Asia. The reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Lao PDR.

Pneumonia and diarrhea are the leading causes of child morbidity and mortality globally and are vaccine preventable. The WHO-coordinated Global Rotavirus and Invasive Bacterial Vaccine-Preventable Disease Surveillance Networks support surveillance systems across WHO regions to provide burden of disease data for countries to make evidence-based decisions about introducing vaccines and to demonstrate the impact of vaccines on disease burden. These surveillance networks help fill the gaps in data in low and middle-income countries where disease burden and risk are high but support to sustain surveillance activities and generate data is low. Through a series of country case studies, this paper reviews the successful use of surveillance data for disease caused by pneumococcus and rotavirus in informing national vaccine policy in Bangladesh, Armenia and The Gambia. The case studies delve into ways in which countries are leveraging and building capacity in existing surveillance infrastructure to monitor other diseases of concern in the country. Local institutions have been identified to play a critical role in making surveillance data available to policymakers. We recommend that countries review local or regional surveillance data in making vaccine policy decisions. Documenting use of surveillance activities can be used as advocacy tools to convince governments and external funders to invest in surveillance and make it a priority immunization activity.

ABSTRACTObjectivesAustralia's Childhood Immunisation Register (ACIR) is one of only a handful of national immunisation registers world-wide. We have, for the first time, linked the ACIR to other health datasets to measure the real-world impact of Australia's immunisation program. In this study, we aimed to assess the population-based effectiveness of the 3-dose infant pneumococcal vaccination program (due at 2, 4, and 6 months) against invasive pneumococcal disease caused by the 7 vaccine specific serotypes. The 7-valent pneumococcal conjugate vaccine (PCV7) has been available since 2001 and a funded universal program started in 2005 (with a switch to 13-valent PCV in 2011). ApproachVaccination records from ACIR, death records, and invasive pneumococcal disease notifications for 2001-2013 were individually linked for 1.37 million children born in 2001-2012 in two Australian states (Western Australia and New South Wales). A Cox proportional hazards model (adjusting for sex, Indigenous status and year of birth) was used to estimate the hazard ratio for invasive pneumococcal disease in vaccinated compared to unvaccinated children less than 2 years old. The per cent of disease prevented by vaccination, or vaccine effectiveness, was calculated as (1-adjusted hazard ratio) x 100%. ResultsFrom 2005, vaccination coverage with dose 3 of the pneumococcal vaccine was steady at ~91% in eligible cohorts. Between 2001 and 2013, there were 468 notifications of invasive pneumococcal disease caused by the 7 vaccine specific serotypes during 2.66 million person years of observation; only 39 (8.3%) of these cases occurred after the universal program was implemented. Vaccine effectiveness against invasive pneumococcal disease caused by the 7 vaccine specific serotypes for 1, 2 and 3 doses of the pneumococcal vaccine was 68% (95%CI: 44-89%), 93% (81-97%), and 92% (95%CI: 86-93%), respectively. ConclusionThis is the first study to link Australia's national immunisation register and measure population-based vaccine effectiveness. The study provides robust evidence of the effectiveness of at least 2 doses of pneumococcal vaccine against vaccine serotype specific infection using a 3 dose infant schedule.

BACKGROUND: The indirect effects of pneumococcal conjugate vaccines (PCVs) are mediated through reductions in carriage of vaccine serotypes. Data on PCVs in Asia and the Pacific are scarce. Fiji introduced the ten-valent PCV (PCV10) in 2012, with a schedule consisting of three priming doses at 6, 10, and 14 weeks of age and no booster dose (3 + 0 schedule) without catch-up. We investigated the effects of PCV10 introduction using cross-sectional nasopharyngeal carriage surveys. METHODS: We did four annual carriage surveys (one pre-PCV10 and three post-PCV10) in the greater Suva area in Fiji, during 2012-15, of 5-8-week-old infants, 12-23-month-old children, 2-6-year-old children, and their caregivers (total of 8109 participants). Eligible participants were of appropriate age, had axillary temperature lower than 37°C, and had lived in the community for at least 3 consecutive months. We used purposive quota sampling to ensure a proper representation of the Fiji population. Pneumococci were detected by real-time quantitative PCR, and molecular serotyping was done with microarray. FINDINGS: 3 years after PCV10 introduction, vaccine-serotype carriage prevalence declined, with adjusted prevalences (2015 vs 2012) of 0·56 (95% CI 0·34-0·93) in 5-8-week-old infants, 0·34 (0·23-0·49) in 12-23-month-olds, 0·47 (0·34-0·66) in 2-6-year-olds, and 0·43 (0·13-1·42) in caregivers. Reductions in PCV10 serotype carriage were evident in both main ethnic groups in Fiji; however, carriage of non-PCV10 serotypes increased in Indigenous Fijian infants and children. Density of PCV10 serotypes and non-PCV10 serotypes was lower in PCV10-vaccinated children aged 12-23 months than in PCV10-unvaccinated children of the same age group (PCV10 serotypes -0·56 [95% CI -0·98 to -0·15], p=0·0077; non-PCV10 serotypes -0·29 [-0·57 to -0·02], p=0·0334). INTERPRETATION: Direct and indirect effects on pneumococcal carriage post-PCV10 are likely to result in reductions in pneumococcal disease, including in infants too young to be vaccinated. Serotype replacement in carriage in Fijian children, particularly Indigenous children, warrants further monitoring. Observed changes in pneumococcal density might be temporal rather than vaccine related. FUNDING: Department of Foreign Affairs and Trade of the Australian Government through the Fiji Health Sector Support Program; Victorian Government's Operational Infrastructure Support Program; Bill & Melinda Gates Foundation.

Background: Invasive alien plant species (IAPs) are plants that have migrated from one geographical region to non-native region either intentional or unintentional.The general view of IAPs in environment is regarded as destructive to the ecosystem and they pose threat to native vegetation and species. However, some of these IAPs are utilized by local inhabitants as a substitute for scarce indigenous plants. The aim of the study is to conduct ethnobotanical survey on medicinal usage of invasive plant species in Waterberg District, Limpopo Province, South Africa. Materials and methods: An ethnobotanical survey on invasive plant species was conducted to distinguish species used for the treatment of various ailments in the Waterberg, District in the area dominated by Bapedi traditional healers. About thirty Bapedi traditional healers (30) were randomly selected via the snowball method. A guided field work by traditional healers and a semi-structured questionnaire was used to gather information. The questionnaire was designed to gather information based on the local name of plants, plant parts used and methods of preparation which is administered by the traditional healers. Results: The study revealed that Schinus molle L., Catharanthus roseus (L.), Datura stramonium L., Opuntia stricta (Haw.) Haw., Opuntia ficus- indica, Sambucus canadensis L., Ricinus communis L., Melia azedarch L., Argemone ochroleuca and Eriobotrya japonica are used for treatment of various diseases such as chest complaint, blood purification, asthma, hypertension and infertility. The most plant parts that were used are 57.6% leaves, followed by 33.3% roots, and whole plant, seeds and bark at 3% each. Noticeably, most of these plants are cultivated (38%), followed by 28% that are common to the study area, 20% abundant, 12% wild, and 3% occasionally. Schinus molle is the most frequently used plant species for the treatment of various ailments in the study area. National Environmental Management Biodiversity Act (NEMBA) (10/2004) and Conservation of Agricultural Resource Act (CARA) were consulted to confirm the invaders status. Only eight plants (60%) are regulated by CARA (10/2004). Of 10 IAPs, 80% (8 species) are listed in both NEMBA and CARA legislation. Only 20% (2 species) are listed in NEMBA alone. Conclusion: Invasive alien plants are utilized by communities to combat various ailments in humans and these plants can help to reduce pressure on heavily harvested indigenous plant.

Abstract Background Effective management of trauma-related invasive fungal wound infections (IFIs) depends on early diagnosis and timely initiation of treatment. We evaluated the utility of routine staining, histochemical stains and frozen section for fungal element identification. Methods A total of 383 histopathological specimens collected from 66 combat-injured United States military personnel with IFIs were independently reviewed by two pathologists. Both periodic acid-Schiff (PAS) and Gomori methenamine silver (GMS) stains were used on 74 specimens. The performance of the two special stains was compared against the finding of fungal elements via any histopathological method (ie, special stains or hematoxylin and eosin). In addition, the findings from frozen sections were compared against permanent sections. Results The GMS and PAS results were 84 % concordant (95 % confidence interval: 70 to 97 %). The false negative rate of fungal detection was 15 % for GMS and 44 % for PAS, suggesting that GMS was more sensitive; however, neither stain was statistically significantly superior for identifying fungal elements ( p = 0.38). Moreover, 147 specimens had frozen sections performed, of which there was 87 % correlation with permanent sections (60 % sensitivity and 98 % specificity). In 27 permanent sections, corresponding cultures were available for comparison and 85 % concordance in general species identification was reported. Conclusions The use of both stains does not have an added benefit for identifying fungal elements. Furthermore, while the high specificity of frozen section may aid in timely IFI diagnoses, it should not be used as a stand-alone method to guide therapy due to its low sensitivity.

Vaccination is undoubtedly one of the most cost-effective child survival public health measure which are more affordable and accessible to community in preventing diseases. Government of India has undertaken several initiatives to strengthen maternal and child health services in the country and child immunisation being an important part of child healthcare system in India. The National Immunization Programme has taken many initiatives since its inception as Expanded Programme on Immunization in 1978. In recent years, there has been introduction of various newer vaccines. Introduction of pneumococcal vaccine in selected states in year 2017 and plan to scale up in the entire country is the newest change in National Immunization Schedule. This review aims to identify various articles related to pneumococcal infection and vaccine highlighting the burden, serotypic distribution, available vaccines, evidence regarding vaccine safety, efficacy, acceptability and cost effectiveness, in order to provide sufficient understanding on the demand and need of this vaccine in India. Important factors underpinned by this article are though there is a need of vaccination due to severe form of pneumococcal infections and antibiotic resistance due to which many developed countries have included PCV in their regular immunisation programmes, however studies regarding effectiveness of pneumococcal vaccines in developing countries like India, data regarding the burden of pneumococcal infections are not available. Also there are limited studies investigating the bacterial and viral etiology of Community Acquired Pneumonia and lack of data to show change in the serotype prevalence overtime. This review highlights the need of more research to provide substantial clinical and epidemiological evidence for the introduction of pneumococcal vaccine.

The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates.

BACKGROUND: Invasive meningococcal disease (IMD) represents a global health burden. However, its epidemiology in the Eastern Mediterranean (EM) and North Africa (NA) regions is currently not well understood. This review had four key objectives: to describe asymptomatic meningococcal carriage, IMD epidemiology (e.g. serogroup prevalence, case-fatality rates [CFRs]), IMD presentation and management (e.g. clinical diagnosis, antibiotic treatments) and economic impact and evaluation (including health technology assessment [HTA] recommendations) in EM and NA. METHODS: A systematic literature search (MEDLINE and EMBASE) was conducted (January 2000 to February 2021). Search strings included meningococcal disease and the regions/countries of interest. Identified publications were screened sequentially by title/abstract, followed by screening of the full-text article; articles were also assessed on methodological quality. Literature reviews, genetic sequencing or diagnostic accuracy studies, or other non-pertinent publication type were excluded. An additional grey literature search (non-peer-reviewed sources; start date January 2000) was conducted to the end of April 2019. RESULTS: Of the 1745 publications identified, 79 were eligible for the final analysis (n = 61 for EM and n = 19 for NA; one study was relevant to both). Asymptomatic meningococcal carriage rates were 0–33% in risk groups (e.g. military personnel, pilgrims) in EM (no data in NA). In terms of epidemiology, serogroups A, B and W were most prevalent in EM compared with serogroups B and C in NA. IMD incidence was 0–20.5/100,000 in EM and 0.1–3.75/100,000 in NA (reported by 7/15 countries in EM and 3/5 countries in NA). CFRs were heterogenous across the EM, ranging from 0 to 57.9%, but were generally lower than 50%. Limited NA data showed a CFR of 0–50%. Data were also limited in terms of IMD presentation and management, particularly relating to clinical diagnosis/antibiotic treatment. No economic evaluation or HTA studies were found. CONCLUSIONS: High-risk ...

The relationship between carriage and the development of invasive meningococcal disease is not fully understood. We investigated the changes in meningococcal carriage in 892 military recruits in Finland during a nonepidemic period (July 2004 to January 2006) and characterized all of the oropharyngeal meningococcal isolates obtained (n = 215) by using phenotypic (serogrouping and serotyping) and genotypic (porA typing and multilocus sequence typing) methods. For comparison, 84 invasive meningococcal disease strains isolated in Finland between January 2004 and February 2006 were also analyzed. The rate of meningococcal carriage was significantly higher at the end of military service than on arrival (18% versus 2.2%; P < 0.001). Seventy-four percent of serogroupable carriage isolates belonged to serogroup B, and 24% belonged to serogroup Y. Most carriage isolates belonged to the carriage-associated ST-60 clonal complex. However, 21.5% belonged to the hyperinvasive ST-41/44 clonal complex. Isolates belonging to the ST-23 clonal complex were cultured more often from oropharyngeal samples taken during the acute phase of respiratory infection than from samples taken at health examinations at the beginning and end of military service (odds ratio [OR], 6.7; 95% confidence interval [95% CI], 2.7 to 16.4). The ST-32 clonal complex was associated with meningococcal disease (OR, 17.8; 95% CI, 3.8 to 81.2), while the ST-60 clonal complex was associated with carriage (OR, 10.7; 95% CI, 3.3 to 35.2). These findings point to the importance of meningococcal vaccination for military recruits and also to the need for an efficacious vaccine against serogroup B isolates.